Benzodioxane derivatives



Patented May 30, 1950 UNITED BENZODIGXEANE DERIVATIVES David 1. Mowry, Dayton, Ohio, assi'gnor-to Monsanto'Cheniical Company, St. Louis, Mo., acorporation of Delaware .No Drawing. Application June 19,1946, Serial No. 6771910 11'!) Claims. 1

:This invention relates to benzodioxane derivatives and provides .2-methyl-4-keto1,3abenzodioxane as a new compound. It also provides a method whereby benzodioxane derivativesmay be prepared by the reaction between o-hydroxyaromatic. acids with vinyl acetate.

I have now found that monomeric vinyl acetate may be.reactedwithany-o-hydroxy aromatic carboxylic acid in the presence .of acidic catalysts or substancesiurnishing hydrogen ions in solution to produce compounds having thestructure:

The scheme for numbering substituents is indicated in the above structural formula.

The o-hydroxy aromatic acids employed in my process may comprise any aromatic nucleus containing the carboxy group and the hydroxy group in adjacent positions in the aromatic ring. As representative of this group of o-hydroxy aromatic acids maybe mentioned those compounds having the followingstructure:

where X is Cl, Br, CH3, N02 and OCH3; Y is H and CH3, X and Y together are benzo. 'Representative materials suitable for the present purpose are: I

Salicylic acid 'Nit r o methylsalicylic Chlorosalicylic acid acid Bromosalicylic acid Methyl .methoxysalicylic Methylsalicylic acid acid I Dimethylsalicyiic acid Methoxysalicylic acid Nitrosalicylic acid 22 hydroxy -3-naphthoic acid 2 hydroxy -l-naphthoic acid,:etc.

It is understood that substituents X and Y may occupyany position inthe .aromatic ring-not .oc- Qupied by the hydroxy and carboxygroup.

The process is preferablycarrie'd out by .re fluxing the o-hydroxy aromatic acid with an excess of vinyl acetate in the presence oiamaterial supplying hydrogen ions. Substances. supplying hydrogen ions are any acid or acid salt such as .2 H2504, benzene sulfonic acid,i.HCl, HNOa, :HsPfih, NaI-ISOr, CHfiCOOH, BF: or ZIlClz. It is obvious thatother acids willoccur to oneskilled. in the art.

Mercuric acetate maybe employed or not=as desired.

Temperatures necessary for carrying out thereaction may range from room temperature to the boiling temperature of the reaction mixture at normal atmospheric pressure, although if 'd'esired higher temperatures may be employed by increasing the *pressureupon the boiling mixture. In this way the timeofreaction -may be considerably shortened.

Since vinyl acetate is a polymerizabl'e ester, it maybe ..desirable. to employ .an inhibitor of poly-. merization in Lthe reaction mixture. .According'rto my' understandingzof the process, the polymerization inhibitor does not affect the main reaction taking place. It, however, serves to prevent polymerization of the vinyl acetate from occurring and enables one to recover the unreacted vinyl acetate for use in a subsequent operation.

The invention is illustrated by the following examples:

EXAMPLE 1 A mixture consisting of 138 g. (1.0mol) of salicylic acid, 258 g. (3.0 mols) of vinyl acetate, 4.0 gofmercuric acetateand 0L5 ccpofsulfuric acid wasrefluxed for aperiod of 36 hours. At the end of this time the excess vinyl acetate and. acetic acid .present were separated from the reaction mixture bydistillation at a pressureof 200 mm. of mercury. The remainder was subsequently distilled ata pressureof 30mm. of mercury, employing a 50 cm. 'Vigreux column. There was obtained. a crude fraction, B. P. 153-160 C130 mm.

a Two redistillations of this fraction gave 87 g.

Percent C PercentH calcd 65. 86 4. 91 found 65. 5. 07

A5 g. sampleof the 2-methyle4-wketo-1,3-benzodioxane washydrolyzed by refluxing it withalcoholic potassium hydroxide. QlThe effluent gas;

tified by melting point and mixed melting point with an authentic sample of salicylic acid.

In the above example, an excess of vinyl acetate was employed to serve as a diluent for the re- 4 EXAMPLE 2 2 methyl-4-keto 8 methoxy 1,3 benzodioxane.-A mixture of 134 g. (0.8 mol) of 3-methoxy salicylic acid, 206 g. (2.4 mole) of vinyl acetate, 4 g. of mercuric acetate, 0.5 cc. of sulfuric acid and 2 g. of hydroquinone were refluxed gently in a water bath. The acid dissolved in about one hour and the material was refluxed for an additional period of eight hours. Disactants. However, any liquid material which is 10 tmation under reduced pressure gave 95 of inert under the reaction conditions may be used crude product, 3 R 1524545 J2 mm" which as Solvent or dlluelit; If vlolenfi be solidified in the receiver. Two recrystallizations employed the reflctlon may be earned out m the from dilute alcohol using Nuchar (a decolorizing absence Solventcarbon) gave 75 g. (49%) of 2-methyl-4-keto- Crystallization of the 2-methyl-4-keto-1,3- 15 3 methoXy 1 3 benzodioxane M P 5 benzodioxane is facilitated by seeding.

The product is a white, crystalline powder hav- EXAMPLE 3 ing a pleasant aromatic odor and a taste reminis- A mixture f 912 of Salicylic acid, 1730 of cent of oil of W nterg It is useful as a physvinyl acetate, 10 g. of tertiary butylcatechol was iolog c y active material. as a perfume ingre- 2O warmed to refluxing temperature, 8 cc. of HzSO4 client and as an insecticide. slowly added and refluxing continued for thirty- As an insecticide, it is particularly valuable Six hours The product was filtered and because it has the property 0f dissolvlng DDT jected to fractional distillation. The fraction (1, triCh10T0-2,2-bi$ D-0h10r0phenyD ethane) boiling above 103 C. at 21 mm. pressure was coland enables one to pro ce compound insecticides 25 lected and then refractionated. The product useful for ce p p Where DDT does not boiling between 95 and 109 at 2.5 mm. was colgive satisfactory results. It is particularly valum t The product was cooled, seeded and a able as a knock-down agent for flies and is also crystal yield of 506 g. of 2-methyl-4-keto-L3-benvaluable in combating red spiders. It has been zodioxane recovered. found that DDT is soluble to the extent of from In a manner illustrated by the above example, 43-45 g. per 100 ml. of 2-methyl-4-keto-1,3benvinyl acetate was reacted with chlorosalicylic zodioxane at 23-25 0., thus enabling the prepacid, bromosalicylic acid, methylsalicylic acid, aration of fairly concentrated solutions to be chloromethylsalicylic acid, nitrosalicylic acid, carried out. methoxysalicylic acid, thiosalicylic acid and 2-hy- The present product has a melting point droxy-3-naphthoic acid. slightly below body temperature, and in addition Th foll w n t ble s mmarizes the chemical a pronounced tendency to supercool. It remains a a d pon e var ous benzodioxanes a liquid when applied to the body. It may, acprepared according to the present invention:

Table Analyses 4-Keto-l, S-benzodioxanes Formula Yield 1 M. P. B P g g Per Calcd. Found Calcd. Found Per cent C'. C'Jm'm. 2-Methyl 60 33 97-98/1 65. 86 65.80 4.91 5.07 2,8-Dirnethyl 25 86-87 164-6/25 67.4 67.4 5.63 5.54 2-Methyl-6-chloro 95-6 160/7 54.8 54.7 3.98 3.53 2-Methyl-G-bron1o 14 84-85 14s-150/5 44.5 44.6 2.88 a. 10 2,8-Dimethyl-frchloro 0101140104.-.- 15 130 56.5 56.6 4. 23 4.43 2-Methyl-6-nitro--- 041171105- 17 111-112 182/4 51.7 51.7 3.25 3.42 2-Methyl-8'Inetl1oxy 0 111004.-- 49 152-154/2 61.9 62.1 5.19 5.28 2-Methyl-4-ketonaphthol-[2,3]-l,3-dioxane 013E100: 41 91-92 185/2 72.9 73.2 4.67 5.09

1 Yield of pure product. Crude yields were often much higher.

' Calcd. for C1; 17.87%. Found: 17.62%. 3 Yield low because of explosion during distillation.

cordingly, also be employed as an insectifuge, since it has a sufliciently high vapor pressure to This application is a continuation-in-part of my application Serial No. 595,067, filed May 27,

give a noticeable odor which, while pleasant to 50 1945, now abandoned.

humans, is objectionable to insects. Against two types of mosquitoes, it showed the following repellent effect (time to first bite).

Aedes aegypti Aedes guadrimaculatus N o. of Repellent No. of Repellent Tests Range Time Tests Range Time Minutes Minutes 8 51-399 242 8 30-152 76 When. employed as an insecticide or as an insectifuge, it may be mixed with suitable carriers such as solvents, diluents or combined with drypowdery material in any proportion.

What I claim is: 1. Compounds having the general formula:

O il/L c :noH4 0 where X is selected from the group consisting of 3. 2-methyl-6-chloro 4 keto 1,3 benzodi-f 4. 2-methy1 8 methoxy 4 keto-1,3-benzodioxane.

5. The process which comprises mixing and heating together under reflux vinyl acetate and an o-hydroxy aromatic carboxylic acid in the presence of an acidic catalyst and recovering a benzodioxane from the reaction mixture.

6. The process which comprises heating under reflux a mixture of vinyl acetate and an o-hydroxy aromatic carboxylic acid in the presence of a catalytic amount of sulfuric acid and recovering a benzodioxane from the reaction mixture.

7. The process which comprises heating under reflux a mixture including an excess of vinyl acetate together with an o-hydroxy aromatic carboxylic acid in the presence of a catalytic amount of an inorganic acid and recovering a benzodioxane from the reaction mixture.

8. The process which comprises heating under reflux a mixture of vinyl acetate and salicylic acid in the presence of a catalytic amount of an acid and recovering 2-methyl-4-keto-1,3-benzodioxane from the reaction mixture.

9. The process which comprises heating under reflux a mixture of vinyl acetate and an o-hydroxy aromatic carboxylic acid in the presence of a polymerization inhibitor and a catalytic amount of sulfuric acid and recovering a benzedioxane from the reaction mixture.

10. An insecticidal or insectifugal composition containing as its active ingredient 2-methyl-4- 1 eto-1,3-benzodioxane and a carrier therefor.

DAVID T. MOWRY.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,047,675 Dupont July 14, 1936 2,245,131 Hermann et a1. June 10, 1941 2,269,272 Krefft -1 Jan. 6, 1942 2,406,504 Morey Aug. 27, 1946 2,409,134 Lecher Oct. 8, 1946 OTHER REFERENCES 

1. COMPOUNDS HAVING THE GENERAL FORMULA:
 10. AN INSECTICIDAL OR INSECTIFUGAL COMPOSITION CONTAINING AS ITS ACTIVE INGREDIENT 2-METHYL-4KETO-1,3-BENZODIOXANE AND A CARRIER THEREFOR. 